Objective: Our previous research on the interaction of chemical carcinogens with transforming system and the naturally-synchronous plasmodium, Physarum polycephalum, we have obtained clear physicochemical and genetic evidence of repair of lesions induced in DNA by such carcinogens. Since chemical carcinogens are strongly implicated causally in human cancer, we have developed a system for quantitating the cytotoxic and mutagenic effects of carcinogens in normal diploid human cells in culture and in cells which are defective in DNA repair capabilities and for determining the role of DNA repair on such interaction. With this system, we are investigating several well- characterized actions of carcinogens: viz:: 1. the effect of carcinogen pre-treatment of normally-repairing diploid human cells or repair-deficient human cells on the expression of viral specific information and/or the ability to be transformed by exposure to DNA tumor viruses, DNA of such viruses, or exogenous DNA containing viral sequences of RNA tumor viruses. 2. the relationship between carcinogens and co-carcinogens in interacting with human cells to cause cytotoxic and mutagenic effects and induce DNA repair. 3. the role of the cell cycle phase on the interaction of carcinogens with synchronized populations of diploid human cells with different repair capabilities. 4. the ability of agents which induce activating enzymes to increase the extent of cytotoxic and mutagenic interaction of carcinogens with these cells. Approach: Such studies give information on the fundamental interaction of carcinogens with human cells and may provide insight as to why such cells are refractory to chemical transformation in vitro, but susceptible to transformation by tumor viruses. These investigations are supported by in vitro and in vivo studies with the B. subtilis and P. polycephalum model systems on relationships between repair and carcinogen attack of DNA.